MaTu is a novel quasi-viral agent with rather unusual properties [Zavada, J., Arch. Virol. 50: 1-10 (1976)]. It is presumably derived from a human mammary tumor. In some respects, it resembles classical viruses whereas in other respects, it resembles "slow" viruses (prions), and in still other respects it is different from both classes of viruses.
MaTu was first detected by its capacity to complement mutants of vesicular stomatitis virus (VSV) with heat-labile surface G protein in HeLa cells (cell line derived from human cervical adenocarcinoma), which had been cocultivated with human breast carcinoma cells. The complementation resulted in the formation of phenotypically mixed virions--the VSV(MaTu) pseudotypes [Zavada et al., Nature New Biol. 240: 124-125 (1972)]. The virions contain the VSV genome, which is responsible for their ability to produce plaques (as well as internal VSV proteins), but the surface protein, corresponding to MaTu, determines their host range and neutralization specificities.
One of the paradoxical features of the MaTu agent is its host range. VSV(MaTu) is infectious only for human fibroblasts, but not for HeLa; however, the MaTu agent, detected by its capacity to donate surface protein for the VSV(MaTu) pseudotypes, is transmissible only to HeLa, but not to fibroblasts [Zavada et al., J. Gen. Virol., 24: 327-337 (1974)].
By its complementation of VSV mutants and by its formation of pseudotypes, MaTu resembles known enveloped viruses. However, MaTu is transmissible only by direct cell-to-cell contact, and not by cell-free filtrates, thus differing from both classical and "slow" viruses. Its only permissive host appears to be HeLa cells. In those cells, MaTu spreads extremely slowly, and does not form morphologically distinct virions, thus resembling the "slow" viruses. [Zavada et al., (1974); Zavada and Zavadova, Arch. Virol. 118: 189-197 (1991)]. No known virus has HeLa cells as an exclusive host.
Since the above-described properties suggest that MaTu might be an entirely new type of molecular parasite of living cells, and since it possibly originated from a human tumor, there was a significant medical research interest to characterize it in more detail. Herein elucidated is the biological and molecular nature of MaTu. MaTu was found to be a two-component system, having an exogenous transmissible component, MX, and an endogenous cellular component, MN. The MN gene was further found to be present in the chromosomal DNA of all vertebrates tested, and its expression was found to be strongly correlated with tumorigenicity.
Described herein is the cloning and sequencing of the MN gene and the production of a MN-encoded protein in a bacterial vector. That genetically engineered MN protein as well as other MN proteins/polypeptides, can be used in serological assays according to this invention to detect MN-specific antibodies. Further, such MN proteins/polypeptides and antibodies reactive with MN antigen can be used in immunoassays according to this invention to detect and/or quantitate MN antigen. Such assays may be diagnostic and/or prognostic for neoplastic and/or pre-neoplastic disease.